Biomarkers of inflammation across the lung to brain axis as mediators of the adverse impacts of air pollution on brain health

最近的流行病学证据表明，从童年早期的认知障碍到青春期到成年期的精神健康不良，以及老年痴呆症风险的增加，空气污染暴露在整个生命过程中都会对神经系统产生影响。在这项提案中，我们将调查空气污染的不利影响是否通过肺到脑的轴来调节。我们认为吸入污染物气雾剂后的肺部炎症驱动全身反应，这些反应通过血脑屏障转化到大脑。该博士学位与UKRI资助的“通过机械毒理学评估室内和室外空气污染物暴露对健康影响的危险识别平台”项目相一致，在该项目中，老年人将暴露在不同来源的特定污染物气溶胶中：柴油废气、木烟和半有机气溶胶和烹饪气溶胶。将对这些人的血液和鼻腔冲洗样本进行分析，以确定全身和神经炎症的标志。此外，样品将被用来利用LC-MS/核磁共振代谢组学方法和循环microRNA分析来研究暴露和反应的新生物标记物。该项目将在MRC环境与健康、分子签名和疾病途径中心主题下进行，建立在之前欧盟资助的暴露组学项目的基础上。预计该项目将在基于实验室的分析和生物信息学/高级统计分析之间平分秋色。

Recent epidemiological evidence has demonstrated neurological impacts of air pollution exposure across the life course, from early cognitive deficits in childhood, to poor mental health across adolescence to adulthood and increased dementia risk in old age. In this proposal we will investigate whether the adverse effects of air pollution are mediated via a lung to brain axis. We propose that pulmonary inflammation following inhalation of pollutant aerosols drives systemic responses that are translated to the brain across the blood brain barrier. This PhD aligns with the UKRI funded 'Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology' project, in which aged individuals will be exposed to different source specific pollutant aerosols: diesel exhaust, woodsmoke and semi organic aerosol and cooking aerosols. Blood and nasal lavage samples from these individuals will be analysed for both established markers of systemic and neuroinflammation. In addition samples will be used to investigate novel biomarkers of exposure and response using LC-MS/NMR metabolomic approaches and analysis of circulating microRNA. This project will be delivered under the MRC Centre for Environment and Health, Molecular Signatures and Disease Pathways theme, building on the previous EU funded Exposomics project. It is envisaged that the project will have an equal split between lab-based analysis and bioinformatics/advanced statistical analysis.